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Title: Activation by insulin and amino acids of signaling components leading to translation initiation in skeletal muscle of neonatal pigs is developmentally regulated

Author
item Suryawan, Agus
item ORELLANA, RENAN - BAYLOR COLLEGE MED
item NGUYEN, HANH - BAYLOR COLLEGE MED
item JEYAPALAN, ASUMTHIA - BAYLOR COLLEGE MED
item FLEMING, JILLIAN - BAYLOR COLLEG MED
item Davis, Teresa

Submitted to: American Journal of Physiology - Endocrinology and Metabolism
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 9/12/2007
Publication Date: 12/1/2007
Citation: Suryawan, A., Orellana, R.A., Nguyen, H.V., Jeyapalan, A.S., Fleming, J.R., Davis, T.A. 2007. Activation by insulin and amino acids of signaling components leading to translation initiation in skeletal muscle of neonatal pigs is developmentally regulated. American Journal of Physiology - Endocrinology and Metabolism. 293(6):E1597-E1605.

Interpretive Summary: Skeletal muscle grows at a very rapid rate in newborn pigs. This is due, in part, to the skeletal muscle's higher sensitivity to make more proteins from amino acids that are obtained after eating. The regulation of muscle protein synthesis is developmentally regulated. In this study, we found that the protein synthesis signals are activated by insulin and amino acids; however, insulin is found to be higher in 7-day-old pigs than 26-day-old pigs. Insulin affects the signaling mechanism to a greater degree than does amino acids. In conclusion, newborn pigs make muscle protein better than older pigs. This is partly due to the higher activation of protein synthesis by insulin versus amino acids.

Technical Abstract: Insulin and amino acids act independently to stimulate protein synthesis in skeletal muscle of neonatal pigs, and the responses decrease with development. The purpose of this study was to compare the separate effects of fed levels of INS and AA on the activation of signaling components leading to translation initiation and how these responses change with development. Overnight-fasted 6- (n = 4/group) and 26-day-old (n = 6/ group) pigs were studied during 1) euinsulinemic-euglycemiceuaminoacidemic conditions (controls), 2) euinsulinemic-euglycemichyperaminoacidemic clamps (AA), and 3) hyperinsulinemic-euglycemic-euaminoacidemic clamps (INS). INS, but not AA, increased the phosphorylation of protein kinase B (PKB) and tuberous sclerosis 2 (TSC2). Both INS and AA increased protein synthesis and the phosphorylation of mammalian target of rapamycin (mTOR), ribosomal protein S6 kinase-1, and eukaryotic initiation factor (eIF)4E-binding protein 1 (4E-BP1), and these responses were higher in 6-day-old compared with 26-day-old pigs. Both INS and AA decreased the binding of 4E-BP1 to eIF4E and increased eIF4E binding to eIF4G; these effects were greater in 6-day-old than in 26-day-old pigs. Neither INS nor AA altered the composition of mTORC1 (raptor, mTOR, and GbetaL) or mTORC2 (rictor, mTOR, and GbetaL) complexes. Furthermore, neither INS, AA, nor age had any effect on the abundance of Rheb and the phosphorylation of AMP-activated protein kinase and eukaryotic elongation factor 2. Our results suggest that the activation by insulin and amino acids of signaling components leading to translation initiation is developmentally regulated and parallels the developmental decline in protein synthesis in skeletal muscle of neonatal pigs.